Modified bacteria may be useful in treating diabetes

“Breakthrough pill can cure diabetes,” is the completely misleading report in the Daily Express.

While researchers have achieved some level of success in using bacteria to improve diabetes control in rats, this in no way amounts to a cure for humans.

The rats had an equivalent of type 1 diabetes, where the pancreas fails to produce the insulin needed by the body to regulate glucose.

The rats were given a daily pill of a genetically modified bacterium. This engineered bacterium secreted a compound that converted cells in the lining of the gut to produce insulin.

After 90 days, these diabetic rats were able to reduce blood glucose levels in a similar way to healthy rats. While diabetic rats fed a normal type of this bacterium had 60% lower levels of insulin and were not able to reduce their blood glucose levels adequately.

Though the treated diabetic rats were able to produce more insulin, the overall level of insulin was still half that of normal rats.

This is preliminary research and there are many questions unanswered, such as how many cells might be converted over time. In addition, it should be made clear that this was not a probiotic pill. This was a genetically modified bacterium.

And, even assuming the engineered bacterium was safe to use in humans, an increase in insulin levels, while welcome, does not amount to a cure for diabetes.

Where did the story come from?

The study was carried out by researchers from Cornell University, New York and was funded by the US National institutes of Health and the Hartwell Foundation. A conflict of interest has been declared by one of the authors as he is involved with a company that has licensed this technology.

The study was published in the peer-reviewed medical journal Diabetes.

The pill is not strictly a “probiotic” as reported by the media. Probiotics are live bacteria and yeasts that are usually present in the human body. The bacteria in the pill in this study has been genetically engineered to secrete a compound called GLP-1, and it is not known what effects this might have if ingested by humans.

Any talk of a cure for diabetes is highly misleading, and arguably irresponsible, as it may offer false hope to people living with diabetes.

What kind of research was this?

This was an animal study in which diabetic rats were given a daily pill of a modified bacterium to see what effect it had on their glucose and insulin levels.

Insulin regulates the level of glucose in the blood and is produced by beta cells in the pancreas. In type 1 diabetes, the pancreas no longer produces insulin as the beta cells have been destroyed by the body’s immune system, and so insulin injections are required. While people with type 2 diabetes have a reduced response to insulin, so higher levels are needed to maintain healthy blood glucose levels.

Initially the pancreas responds by making extra insulin, but over time this fails. Type 2 diabetes is managed through diet, medication and in some cases, insulin.

Previous research found that a compound called GLP-1 can convert intestinal cells into cells that produce insulin. The problem is that GLP-1 in humans breaks down quickly in the blood (it has a very short half-life) so the challenge is to find a way to move the compound into the intestine.

These experiments were conducted on cells in the laboratory setting. The researchers wanted to see if they could find a way to get GLP-1 to intestinal cells in rats and whether these cells could be reprogrammed as they were in the laboratory.

What did the research involve?

The researchers engineered Lactobacillus, a bacterium that is usually present in the human gut, to secrete a compound called GLP-1. They created a pill of these bacteria and gave it to rats with type 1 diabetes to see if it could deliver GLP-1 to the gut wall. They then investigated whether it changed the type of cells lining the intestine so that they could produce insulin.

Rats with type 1 diabetes were given two pills daily for 90 days of either:

engineered Lactobacillus that secrete GLP-1

normal Lactobacillus

Healthy rats were kept in the same conditions and given a placebo to act as a control.

To test whether the GLP-1 had converted any cells to produce insulin, after 51 days the rats were fasted for 10 hours and then given an injection of glucose. Blood glucose and insulin levels were measured after 30 minutes, one hour, one and a half hours and two hours.

At the end of the 90 days, the cells lining the intestine and the pancreas were examined and the level of gut bacteria was measured.

What were the basic results?

There was no significant difference in the blood glucose or insulin levels in diabetic rats fed engineered Lactobacillus compared with healthy control rats. Whereas diabetic rats fed normal Lactobacillus had higher blood glucose and lower blood insulin levels, as would be expected.

The level of insulin in the intestines of rats fed engineered Lactobacillus was more than five times higher than either of the other groups of rats. These rats had insulin-secreting cells in their intestines that had features of beta cells (the cells that produce insulin in the pancreas). These cells appeared to produce insulin in response to glucose. On average, 0.06% of the intestinal cells had been converted to secrete insulin.

Rats fed engineered Lactobacillus had 60% more total insulin than those fed normal Lactobacillus.

The overall level was half that of the control rats.

How did the researchers interpret the results?

The authors concluded that feeding diabetic rats the genetically engineered bacteria can cause them to produce insulin in response to eating, which significantly reduced their blood glucose levels. They say this appeared to have been produced from cells in the intestine that had been transformed from normal gut cells to insulin secreting cells. The researchers call for further work to be done to fully understand the mechanism involved.

Conclusion

This animal research has shown that a pill of genetically engineered Lactobacillus can convert cells lining the gut into cells that produce insulin in rats. This conversion was made by stimulating the cells with a compound called GLP-1 that was secreted by these modified bacteria that are usually present in the human gut.

The researchers were able to demonstrate that the cells had changed function to become more like the beta cells that usually produce insulin in the pancreas. They also showed that the insulin reduced the rats’ blood glucose levels to that of control rats.

There are a number of questions that need to be addressed before this new technique progresses to primate studies on the long road to becoming a treatment for either form of diabetes. Over the 90 days 0.06% of the intestinal cells were converted but it is unclear whether this proportion would increase over time and whether this depends on the dose of bacteria given. It is also not known whether these cells need daily bacteria to continue to behave like cells from the pancreas or whether the change is permanent and the cells can renew.

There are also unanswered questions about what effect having a reduced number of normal intestinal cells could have on the function of the gut. Finally, it will need to be determined how any such cell renewal is controlled so that it does not go into overdrive and produce too many insulin producing cells.

Overall, the results of this preliminary piece of research are encouraging in the search for a possible cure for diabetes, though this is still a long way off.

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